全文获取类型
收费全文 | 91篇 |
免费 | 5篇 |
专业分类
96篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2017年 | 2篇 |
2016年 | 7篇 |
2015年 | 9篇 |
2014年 | 7篇 |
2013年 | 4篇 |
2012年 | 8篇 |
2011年 | 5篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有96条查询结果,搜索用时 15 毫秒
41.
Renee. J. Smith Thomas C. Jeffries Eric M. Adetutu Peter G. Fairweather James G. Mitchell 《PloS one》2013,8(11)
The functional dynamics of microbial communities are largely responsible for the clean-up of hydrocarbons in the environment. However, knowledge of the distinguishing functional genes, known as the metabolic footprint, present in hydrocarbon-impacted sites is still scarcely understood. Here, we conducted several multivariate analyses to characterise the metabolic footprints present in a variety of hydrocarbon-impacted and non-impacted sediments. Non-metric multi-dimensional scaling (NMDS) and canonical analysis of principal coordinates (CAP) showed a clear distinction between the two groups. A high relative abundance of genes associated with cofactors, virulence, phages and fatty acids were present in the non-impacted sediments, accounting for 45.7 % of the overall dissimilarity. In the hydrocarbon-impacted sites, a high relative abundance of genes associated with iron acquisition and metabolism, dormancy and sporulation, motility, metabolism of aromatic compounds and cell signalling were observed, accounting for 22.3 % of the overall dissimilarity. These results suggest a major shift in functionality has occurred with pathways essential to the degradation of hydrocarbons becoming overrepresented at the expense of other, less essential metabolisms. 相似文献
42.
Diahann TSL Jansen Hanane el Bannoudi Ramon Arens Kim LL Habets Marjolijn Hameetman Tom WJ Huizinga Jeroen N. Stoop René EM Toes 《Arthritis research & therapy》2015,17(1)
IntroductionAbatacept is a fusion protein of human cytotoxic T-lymphocyte–associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1). It is believed to be effective in the treatment of rheumatoid arthritis by inhibiting costimulation of T cells via blocking CD28–B7 interactions as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 molecules is crucial for activation of naive cells, whereas it is unclear whether the action of already activated CD4+ T cells, which are readily present in established disease, also depends on this interaction. The aim of this study was to determine whether the mode of action of abatacept depends solely on its ability to halt T cell activation in established disease.MethodsArthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4+ T cells. Abatacept or control treatment was started when 80 % of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws, and anti-collagen antibody levels over time were determined by enzyme-linked immunosorbent assay.ResultsTreatment with abatacept in the absence of CD4+ T cells resulted in lower disease activity. This was associated with decreasing levels of collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in control or CD4+ T cell–depleted mice increased over time.ConclusionsThese results show that abatacept decreased disease activity in the absence of CD4+ T cells, indicating that the mode of action of abatacept in established arthritis does not depend entirely on its effects on CD4+ T cell activation. 相似文献
43.
WalterDuartedeAraujo Filho Fábio Kurt Schneider Rigoberto EM Morales 《Biomedical engineering online》2012,11(1):1-14
Background
In recent years magnesium alloys have been intensively investigated as potential resorbable materials with appropriate mechanical and corrosion properties. Particularly in orthopedic research magnesium is interesting because of its mechanical properties close to those of natural bone, the prevention of both stress shielding and removal of the implant after surgery.Methods
ZEK100 plates were examined in this in vitro study with Hank's Balanced Salt Solution under physiological conditions with a constant laminar flow rate. After 14, 28 and 42 days of immersion the ZEK100 plates were mechanically tested via four point bending test. The surfaces of the immersed specimens were characterized by SEM, EDX and XRD.Results
The four point bending test displayed an increased bending strength after 6 weeks immersion compared to the 2 week group and 4 week group. The characterization of the surface revealed the presence of high amounts of O, P and Ca on the surface and small Mg content. This indicates the precipitation of calcium phosphates with low solubility on the surface of the ZEK100 plates.Conclusions
The results of the present in vitro study indicate that ZEK100 is a potential candidate for degradable orthopedic implants. Further investigations are needed to examine the degradation behavior. 相似文献44.
45.
46.
Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units 总被引:1,自引:0,他引:1 下载免费PDF全文
EH Larsen SE Gabriei MJ Stutts J Fullton EM Price RC Boucher 《The Journal of general physiology》1996,107(6):695-714
The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units. 相似文献
47.
48.
49.
YK Onno Teng Gillian Wheater Vanessa E Hogan Philip Stocks EW Nivine Levarht Tom WJ Huizinga Rene EM Toes Jacob M van Laar 《Arthritis research & therapy》2012,14(2):R57
Introduction
B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells.Methods
In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients.Results
Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion.Conclusion
By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells. 相似文献50.